Anosognosia in hoarding disorder is predicted by alterations in cognitive and inhibitory control

Insight impairment contributes significantly to morbidity in psychiatric disorders. The neurologic concept of anosognosia, reflecting deficits in metacognitive awareness of illness, is increasingly understood as relevant to psychopathology, but has been little explored in psychiatric disorders other than schizophrenia. We explored anosognosia as an aspect of insight impairment in n = 71 individuals with DSM-5 hoarding disorder. We used a standardized clutter severity measure to assess whether individuals with hoarding disorder underreport home clutter levels relative to independent examiners. We then explored whether underreporting, as a proxy for anosognosia, is predicted by clinical or neurocognitive behavioral measures. We found that individuals with hoarding disorder underreport their clutter, and that underreporting is predicted by objective severity of clutter. In an n = 53 subset of participants, we found that underreporting is predicted by altered performance on tests of cognitive control and inhibition, specifically Go/No-Go and Stroop tests. The relation of underreporting to objective clutter, the cardinal symptom of hoarding disorder, suggests that anosognosia may reflect core pathophysiology of the disorder. The neurocognitive predictors of clutter underreporting suggest that anosognosia in hoarding disorder shares a neural basis with metacognitive awareness deficits in other neuropsychiatric disorders and that executive anosognosia may be a transdiagnostic manifestation of psychopathology.

Overview and behavioral assessment of anosognosia. Demographic and clinical data were collected from participants screening for participation in a clinical treatment study of HD between October 2016 and April 2019 (Fig. 1A). Participants self-identified as seeking help with clutter and were recruited via targeted online advertisements, radio advertisements, local flyering, and word of mouth. Clinical data included self-and clinician-rated assessments performed either in clinic, via secure teleconference, or via secure web-based submission portals. After initial assessments, a home visit was scheduled during which an IE rated home clutter severity (Fig. 1B). The full n = 71 study sample includes all participants for whom both self-and home-visit IEratings of clutter were completed during the recruitment period.
A quantitative behavioral measure of anosognosia was generated by evaluating the discrepancy between selfratings of clutter made using the CIR, a validated pictographic instrument 48 , and objective (IE) ratings of clutter using the same instrument, as a proportion of total objective clutter score (see "Assessments" and "Statistical analysis" below).
Inclusion/exclusion. To qualify for a home visit (and thus to be included in the n = 71 study sample), participants were required to meet the following inclusion criteria: age between 18-75; primary DSM-5 HD diagnosis (assessed via the structured clinical interview (SCID) for DSM-5) 49 ; clinically significant symptoms (defined as a Saving Inventory-Revised (SI-R) score ≥ 40) 50 ; no or stable psychotropic medication use (defined as medication doses unchanged for > 4 weeks prior to assessment or > 8 weeks if fluoxetine); a safely accessible home in one of two neighboring counties and within 30 miles of Stanford University. Participants were excluded if they had OCD as a primary diagnosis, a current or history of psychotic disorder or bipolar disorder, a current eating disorder, or a current moderate or lifetime severe substance use disorder. Patients were additionally excluded if they had current severe depression (defined as Hamilton Depression Rating Scale (HDRS) score > 30) 51 , had any other medical or neuropsychiatric condition that would increase risk of participation or interfere with engagement in assigned behavioral practice tasks, were currently working with a professional organizer, or were at elevated acute eviction risk. For one participant, a full SCID was completed only after the home visit occurred; however, given the availability of both self-and IE-CIR ratings data, this individual was included in the analysis despite bipolar disorder comorbidity. Similarly, two participants who for scheduling reasons underwent a home visit prior to completing the SI-R, and who were found to have SI-R < 40 (with scores of 14 and 37), were nonetheless included in the analysis given the availability of both self-and IE-CIR ratings and diagnosis of HD per SCID.
Assessments. The CIR 48 is a validated pictorial scale of clutter severity consisting of nine photographs each of an increasingly cluttered kitchen, bedroom, or living room. Each room in a home is rated by choosing the image that most closely corresponds to the level of clutter in the room, and a composite home score is generated by averaging room scores. The CIR is designed for use by both patients and clinicians. As validated, the composite CIR score has high test-retest reliability (r = 0.85 when repeated by patients with interval of < 2 months) and high inter-observer reliability (r = 0.94) when both patient and clinician are in the home being rated; cor-  71 participants completed an in-home evaluation during which independent evaluators (IEs) rated home clutter levels using the CIR, thus allowing a measure of anosognosia based upon the relative discrepancy of self-vs IE-rated clutter. (C) 53 participants for whom a measure of anosognosia was obtained proceeded to the clinical treatment study and completed computer-based neurocognitive testing (WebNeuro). www.nature.com/scientificreports/ relation between asynchronous patient ratings made in the clinic and clinician ratings made in the home is less strong (r = 0.78) 48 , as similarly observed in an independent study of older adults (r = 0.54) 52 . Our data included asynchronous participant CIR ratings (self-CIR) made in clinic and independent examiner CIR ratings (IE-CIR) made during a subsequent home visit. Composite scores for both self-CIR and IE-CIR were calculated by averaging scores from only those rooms rated by both participant and IE. The SI-R 50 is a 23-item questionnaire using a 5 point (0 to 4) Likert-type scale that assesses severity of compulsive hoarding. It comprises three subscales defined by exploratory factor analysis, reflecting core domains of hoarding behavior, including Excessive Acquisition (seven items), Difficulty Discarding (seven items), and clutter (nine items). Internal consistency (Cronbach's alpha) for the full scale in our sample was acceptable, at 0.86. Alpha values for the subscales of the SI-R were 0.7 for Difficulty Discarding, 0.88 for Clutter, and 0.79 for Excessive Acquisition.
The Saving Cognitions Inventory (SCI) 53 is a 24-item questionnaire using a 7 point (1 to 7) Likert-type scale that assesses the experienced frequency of thoughts and beliefs related to possessions (e.g., "I am responsible for the well-being of this possession"). Although a measure of beliefs, not of hoarding behaviors per se, the SCI correlates strongly with measures of hoarding 54 . Factor analysis of SCI responses has defined four subscales, including emotional attachment (ten items), memory (five items), control (three items), and responsibility (six items) 53  Neurocognitive testing. A subset of participants (n = 53) met criteria for clinical study enrollment and underwent neurocognitive assessment (Fig. 1C). These criteria included having at least one room IE-CIR rated ≥ 3 on home visit, and having a home deemed safe for ongoing visitation by study staff (i.e., free of mold, vermin, or structural risks).
Neurocognitive assessment of cognitive control was undertaken using a computerized test battery called WebNeuro 58 , which has been validated against gold-standard neuropsychological tests assessing the equivalent constructs 58,59 . The testing battery was completed in a single sitting of approximately 45 min. Participants were offered the opportunity to complete WebNeuro testing either at home or in a private office in the clinic. The neurocognitive domains assessed by this battery and the test used to assess them (and the equivalent test from traditional paper-pencil neuropsychological tests) include: ix. Inhibition; Verbal Interference task assessing capacity to suppress conflicting information when assessing either written word or ink color (Stroop).
Individual performance on each of these behavioral tests was quantified by accuracy and reaction time relative to matched healthy norms for age, sex, and years of education (normative cohort of n = 1317) 60,61 . These normreference scores were expressed as standardized scores with a mean of 0 and standard deviation of 1, such that lower scores reflected greater impairment.
Statistical analysis. Using self-and IE-rated composite CIR scores, we generated an error metric ('CIRerror') for each participant that reflected the degree of under-or over-reporting. Taking the IE-CIR as 'objective, ' we defined CIR-error as self-CIR subtracted from IE-CIR, divided by IE-CIR ((IE-CIR-self-CIR)/IE-CIR), thus capturing discrepancy in self-report in proportion to objective clutter severity. As defined, more positive scores of CIR-error reflect greater underreporting of clutter.
Means, ranges, and standard deviations were assessed for demographic, clinical, and neurocognitive variables. One-sample Student's t-tests with µ = 0 were used to assess differences in neurocognitive performance between our HD participants and the normative population. For those variables for which our participants' scores were not normally distributed, as per Shapiro-Wilk test, we employed a one-sample Wilcoxon Rank Sum Test. An initial alpha threshold of 0.05 was Bonferroni-adjusted for the number of independent predictors.
We assessed relationships between clinical and neurocognitive variables and CIR-error, as well as self-and IE-CIR scores themselves, using univariate linear regression with CIR-error as the dependent variable. To account for multiple comparisons, the alpha threshold was Bonferroni-adjusted for the number of independent predictors tested. Significant predictors of CIR-error were considered as possible explanatory variables in a multiple linear regression model. Proportions of variance explained are provided as adjusted R 2 . Instances of missing data were addressed with listwise deletion; given limited missing observations (< 4 cases per variable), the assumption that data are missing completely at random was not felt to add significant risk of bias. All statistical assessments were performed using R version 4.

Relation of clutter underreporting to clinical assessments.
Other demographic and clinical variables were next assessed as predictors of CIR-error (Table 2). For the full sample, CIR-error was not predicted by age, gender, handedness, psychotropic medication use, number of current somatic medical diagnoses, or depression (HDRS). Notably, clinical measures of HD were also not predictive of CIR-error. Only the Difficulty Discarding subscale of the SI-R (SIR-DD) showed a trend toward prediction of CIR-error-however, with a negative coefficient, such that lower scores on SIR-DD predicted greater underreporting of clutter (β = − 0.02 (95% CI − 0.033 to − 0.003), R 2 = 0.08, p = 0.021). The SCI and its component subscales were similarly not predictive of CIR-error.
Neurocognitive performance. Fifty-three participants completed computer-based neurocognitive testing. Demographic and clinical characteristics of this subset were like those of the full sample (Table 1). Means for normed performance on task measures are represented in Table 3 Relation of clutter underreporting to neurocognitive performance. We next explored neurocognitive performance measures as independent predictors of CIR-error using univariate linear regression ( www.nature.com/scientificreports/ www.nature.com/scientificreports/ regression. This additionally suggested completion time for the Switching of Attention test (β = − 0.06 (95% CI − 0.12 to − 0.01) p = 0.032) as a predictor of CIR-error at a trend level.

Discussion
To our knowledge, our study is the first to assess anosognosia in HD in a manner that does not rely on direct subjective impressions of family or clinician raters and the first study to explore neurocognitive correlates of insight in HD. We found that most participants in our study underrated their clutter, that the degree of underrating was correlated with severity of clutter, and that underrating was correlated with behavioral performance on specific tests of neurocognitive function.
Clutter rating discrepancies. Whether HD patients tend to underreport or overreport symptoms has been explored in prior studies 48,64 . Variable results when comparing self-ratings with other-ratings on diverse measures have suggested that such tendencies may be influenced by motivation or context (e.g., that participants seeking to enroll in studies might overestimate the severity of their disorder) 64 . In our study, however, the underreporting of clutter per self-CIR, performed in the context of screening for study participation, is inconsistent with such motivation. The correlations of this underreporting with objective clutter and with neurocognitive behavioral performance further argue against a purely social or contextual explanation for the discrepancies we observe.
Our study relies on discrepancies in CIR rating when the CIR is used as a self-report measure vs a clinicianrated measure. The close correlation of simultaneous self and clinician ratings reported in the literature suggests against gross differences in perception in individuals with HD. The time elapsed between asynchronous self-and IE-ratings in our study may suggest the possibility of interval change in clutter; yet discrepancies we observed were not correlated with inter-assessment interval. Deficits in memory or updating may explain discrepancies when HD participants perform self-rating outside of their homes, in line with observations that insight deficits in OCD are negatively correlated with verbal memory performance 65 (though not consistently) 66 or visual memory performance 66 . However, in our study, discrepancies in CIR rating were not predicted by behavioral measures of learning or memory.
The lower correlations of asynchronous (relative to synchronous) self and clinician clutter ratings observed in prior studies 48,62 suggests that accuracy of clutter self-assessment, and indeed awareness itself, may be influenced by the presence of a third-party observer. This accords with what has been described in clinical literature, whereby individuals with HD may experience sudden increases in both awareness and distress when others enter their home 26 . Such fluctuating awareness in relation to third-party perspective may accord with findings from anosognosia in hemiplegia, schizophrenia, and dementia, in which unaware patients may be able to acknowledge deficits when exposed to evidence from a third-person perspective. This phenomenon has been modeled conceptually in dementia by invoking activation of distinct systems for autobiographical vs generic memory 67 . Anosognosia as characteristic of hoarding disorder. In our study, participants' underreporting of clutter increased with objective clutter severity, the cardinal symptom of HD, suggesting that anosognosia may reflect core pathophysiological processes of HD. The relation between underreporting of clutter (insight impairment) and objective clutter severity (behavioral outcome) may find analogy in studies of insight in cocaine use disorder, where underreporting of desire to view cocaine-related images (relative to actual choice of such images in a laboratory context) predicted past-30-day cocaine use 68 . Importantly, clutter underreporting had no relation to self-reported clutter severity and was not correlated with self-report scales of HD severity, with the exception of a trend-level negative correlation with the Difficulty Discarding subscale of the SI-R. Absent or anti-correlations with self-report HD severity measures might be expected if underreporting is a true proxy of anosognosia. If anosognosia is common or characteristic of HD, however, this raises nosological questions about how the disorder might best be defined or assessed, i.e., whether to emphasize behavior and behavioral impacts (e.g., acquiring, saving, or clutter) or subjective distress associated with hoarding behaviors. The absence of a correlation between clutter underreporting and subscales of the SCI-which scores strength of agreement with various beliefs related to HD-is also notable, in as much as the best-validated instrument for assessing insight in other OCRDs, the BABS, emphasizes strength of disorder-related beliefs as fundamental to ratings of insight. If, as per prior literature, insight impairment in HD is a multi-dimensional construct with both 'unawareness' (anosognosia) and 'delusionality' as component axes 26,27 , our proxy measure appears to capture anosognosia more so than overvalued ideation or delusionality.
Anosognosia and cognitive control. Errors on a Go/No-Go test of response inhibition most strongly predicted clutter underreporting in our sample. We are the first study to our knowledge to report Go/No-Go performance as a correlate of clinical insight, although in a neuroimaging study, decreased Go/No-Go task- www.nature.com/scientificreports/ based activations of cingulate and prefrontal cortex have been associated with unawareness of deficits in Alzheimer's Disease 69 . As a measure of response inhibition, however, our finding is strongly consistent with replicated findings from research in psychotic disorders correlating deficits in clinical insight with deficits in Wisconsin Card Sort Test performance, and with the suggestion, based on this work, that insight impairment might reflect deficits in cognitive control and a tendency to perseverative error 17 . We additionally identified differential response time on a Stroop color/word task as a predictor of clutter underreporting. Correlations between Stroop performance and clinical insight impairment have been reported for OCD 65 and for bipolar disorder 70 , on which basis insight impairment has similarly been suggested to reflect deficits in response inhibition and the processing of conflictual information. For our participants, we observed that increased clutter underreporting predicted better normalized response time performance on the ink color naming task relative to the word reading task. One speculative consideration is that insight deficits in OCRDs may correspond to deficits in the fast, ventralstream visual pathway required for word recognition and logographic processing. Deficits in such ventral-stream processing for complex figures have been observed to correlate with insight impairment in body dysmorphic disorder 71,72 . Such deficits, if present in our HD participants, might be expected to slow response in the noninterference phase of our Stroop paradigm-which relies on fast reading of written color names-and yet speed performance in the interference phase of our Stroop paradigm, in as much as 'overlearned' word recognition might less potently interfere with ink color naming. Lastly, while below threshold for significance when included in a model with other clinical and neurocognitive predictors, we observed a trend toward impaired performance on the Switching of Attention test as a correlate of clutter underreporting, particularly when controlling for level of clutter. This is consistent with findings from OCD 66,73 , anorexia nervosa 74 , and bipolar disorder 70,75 , in which relative deficits in the Trail Making Test Part B have been found to correlate with impaired clinical insight. The observation that abnormalities of response inhibition, interference processing, and attention switching might correlate with insight impairment across diagnoses supports a general model in which awareness is intrinsically related to cognitive control. Conceptually, a theory of conscious awareness suggests that subjective awareness is a schematic model of attention itself, evolved to facilitate top-down control of attention 76 . Similarly, the CAM model for metacognitive awareness in dementia and other neurologic conditions suggests that deficits in executive error processing-required for the updating of self-concept based on sensory input-may present one pathway for the development of anosognosia 23 . Our data suggesting that pathological unawareness in HD correlates with deficits in cognitive control might provide a novel line of evidence in support of these general models.
Limitations and future directions. Limitations of the current study include its exploratory nature and the possibility of Type I error. Additionally, our help-seeking sample may not be representative of the broader population of individuals with HD in terms of clinical insight: our participants lived in homes that were deemed non-squalorous and safely accessible for research staff, they were predominantly older women, and half were using psychotropic medication. While we suggest CIR-error as a face-valid proxy for anosognosia in HD, as a measure of clinical insight impairment more broadly it may not be fully content-valid, in that it may not capture clinically important dimensions of insight impairment in HD, such as the tendency to misjudge the value of objects or risks of clutter, or propensity to interpersonal distortions, by which individuals offering help may be perceived as threatening 26,27 . We additionally do not assess test-retest reliability of our measure. Nonetheless, the fact that CIR-error correlates with a measure of behavioral severity (objective clutter) and with measures of neurocognitive function identified as correlates of insight impairment in other disorders supports the construct validity of CIR-error as a proxy for anosognosia as a component of insight impairment. Future work could assess whether clutter underreporting correlates with neurophysiologic or neuroimaging measures of error signaling known to be aberrant in OCD 77,78 and HD 46,47 . In particular, in as much as HD-in contrast to OCD-may be associated with diminished, rather than exaggerated error signaling 46,47 , it would be of interest to test whether clutter underreporting correlates negatively with error signaling. This might replicate associations between insight impairment and hypoactive error signaling seen in cocaine use disorder 19 or proposed in anosognosia for hemiplegia 18 . Given the prevalence, morbidity, and adverse prognostic significance of insight impairment across the spectrum of neuropsychiatric illness, and given the paucity of treatment interventions specifically targeting this dimension of illness, identifying the neural basis for insight in HD and other disorders will be critical to developing more effective future treatments for mental health conditions.

Data availability
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available, as they contain information that could compromise the privacy of research participants.